We aim to develop specific and sensitive tests to detect chronic diseases of airways early and to study mechanisms which trigger asthma attacks. The physiologic studies of early diagnosis aim to develop tests which detect subclinical emphysema and differentiate it from other causes of chronic airway obstruction and to determine the morphologic basis of the physiologic abnormalities. A multiple breath analysis of CO uptake using a new, rapid CO meter will be utilized not only to detect mild emphysema, but other disorders affecting pulmonary capillaries (e.g., pulmonary embolism, pulmonary hemorrhage). The radiologic studies aim to establish the efficacy and safety of powdered tantalum as a bronchographic contrast material for detecting early airway disease, for localizing the sites of airway obstruction, and for identifying sites of abnormal mucociliary clearance. Airway hyperirritability appears to be a hallmark of asthma, therefore we will continue to study the mechanism by which epithelial damage induced by viruses, ozone, sulfur dioxide, and other air pollutants causes increased bronchial sensitivity in allergic patients and normal subjects. The neurophysiologic, biochemical, and morphological basis of the clinical findings will be studied in experimental animals. Because interactions between humoral and autonomic nervous mechanisms also play a critical role in the pathogenesis of asthma, we will utilize neurophysiologic, immunologic, pharmacologic and morphologic methods to study these mechanisms in experimentally-induced canine asthma.